Project Summary/Abstract The goal of this training program in environmental toxicology is to produce scientists and engineers professionally qualified to make original contributions to improved understanding of the impacts of environmental agents, especially hazardous chemicals, on human health. This program has supported 112 predoctoral and 94 postdoctoral Trainees since its inception in 1975. During that same time period, 356 PhD or ScD degrees have been awarded to all students in the MIT toxicology program (Trainees plus non- Trainees). Of our pre-doctoral and post-doctoral Trainees over the past 15 years, 8 out of 66 (12%) are in academic positions and 42 (64%) are in industry or government, with the balance continuing in training. Trainees pick projects from the following areas: (1) analysis of genome-, proteome- and glycome-level responses to toxins and toxicants; (2) characterization of mutagenic responses to carcinogens as expressed hierarchically at the genome, cell, tissue, organism and population levels of organization; (3) construction of novel animal models for determining the effects of exposure of mammals to environmental agents; (4) systems biology of kinase-mediated signaling cascades triggered in response to toxic agents, and during neoplastic transformation; (5) characterization of the chemistry underlying the reaction of toxins and toxicants with cellular macromolecules and other targets; (6) mechanistic assessment of the contribution of DNA damage to genetic disease, and identification of the cellular defenses (e.g., DNA repair strategies) that protect against heritable damage; (7) engineering-based design of novel model systems for evaluating responses to toxic agents; (8) unraveling the underlying biology of environmental chemical-infectious agent interactions; and (9) development of analytical methods for monitoring hazardous chemicals in the environment, and determining of how those agents chemically change over time. In the previous period of support, 29% of the PhD students supported were from underrepresented groups, and 59% were female. Regarding postdocs, 18.2% were from underrepresented groups, and 55% of the cohort was female. More than 600 students apply for the pre- doctoral program annually, allowing for good program selectivity. Highlights of the program are a well-structured and constantly updated academic toxicology Certificate Program taken by PhD students, a pre- and post-doctoral mentoring program, numerous toxicology-focused seminar programs and a large emphasis on research collaboration. We created a course entitled Fundamentals of Toxicology and Environmental Health to cross-train our diverse group of engineers and scientists. It includes formal toxicology lectures, training in responsible conduct of research, authentication of reagents, rigor and reproducibility, data science and community outreach. This proposal requests funding for seven predoctoral and six postdoctoral trainees.